Abstract
The metabolic turnover, absolute oral bioavailability, clearance, and volume of distribution for β-sitosterol were measured in healthy subjects. [14C]β-Sitosterol was used as an isotopic tracer to distinguish pulse doses from dietary sources and was administered by both oral and intravenous routes. The administered doses of [14C]β-sitosterol were in the region of 3 to 4 μg, sufficiently low as not to perturb the kinetics of β-sitosterol derived from the diet. Because the plasma concentrations of [14C]β-sitosterol arising from such low doses were anticipated to be very low, the ultrasensitive isotope ratio analytical method of accelerator mass spectrometry was used. The limit of quantification for [14C]β-sitosterol was approximately 0.1 pg/ml, the oral absolute bioavailability was just 0.41%, clearance was 85 ml/h, volume of distribution was 46 L, and the turnover was 5.8 mg/day. Given the steady-state concentrations of β-sitosterol (2.83 μg/ml), then the dietary load was calculated to be approximately 1400 mg/day.
Footnotes
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
ABBREVIATIONS:
- AMS
- accelerator mass spectrometry
- ANU
- Australian National University
- AUC
- area under the plasma concentration-time curve
- CL
- clearance
- CV
- coefficient of variation
- GC-MS
- gas chromatography-mass spectrometry
- HPLC
- high-performance liquid chromatography
- LOQ
- limit of quantification
- pMC
- percent modern carbon
- t½
- elimination half-life
- t½α
- t½β, elimination half-lives for the α and β elimination phases, respectively
- V
- volume of distribution
- Vss
- volume of distribution at steady state.
- Received May 4, 2012.
- Accepted July 23, 2012.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics
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